Tick bite fever (TBF) and Q fever are zoonotic infections, highly prevalent in southern Africa, which are caused by different genera of obligate intracellular bacteria. While TBF was first described nearly 100 years ago, it has only recently been discovered that there are several rickettsial species transmitted in southern Africa, the most common of which is Rickettsia africae. This helps to explain the highly variable clinical presentation of TBF, ranging from mild to severe or even fatal, that has always been recognised. Q fever, caused by Coxiella burnetii, is a protean disease that is probably extensively under-diagnosed. Clinically, it also shows a wide spectrum of severity, with about 60% of cases being clinically inapparent. Unlike TBF, Q fever may cause chronic infection, and a post-Q fever chronic fatigue syndrome has been described. The molecular pathophysiology of these diseases provides insight into different strategies that intracellular parasites may use to survive and cause disease. While newer macrolide and quinolone antibiotics show activity against these pathogens and may be useful in young children and pregnant women, the treatment of choice for acute infection in both diseases is still tetracycline-group antibiotics. Chronic Q fever remains challenging to treat.